Making insulinomas a thing of the past

Kyoto, Japan -- Diabetes is characterized by the pancreas producing too little insulin, but there is a rarer condition in which it produces too much. A hormone-producing tumor originating in the pancreas -- an insulinoma -- is the cause. Patients with the condition often experience severe hypoglycemia, resulting in convulsions, impaired consciousness, and sometimes even death.

The definitive treatment for an insulinoma is surgical removal, which depends on precise localization. However, existing diagnostic methods are limited by low sensitivity or high invasiveness, resulting in urgent clinical demand for a new means of detection.

"As endocrinologists and researchers, we frequently encountered patients experiencing severe hypoglycemia who faced delays or difficulties in obtaining an accurate diagnosis, negatively impacting their quality of life," says first author Takaaki Murakami of Kyoto University.

The team's personal commitment to enhancing patient care and outcomes drove the researchers to explore an imaging approach involving a newly developed positron emission tomography, or PET, probe, focusing on glucagon-like peptide-1 -- GLP-1 -- receptors. Using the probe to target these receptors -- expressed in abundance on insulinoma cells -- they conducted a Phase II clinical trial, enrolling 12 patients with hypoglycemia and clinically suspected to have insulinomas.

After the team performed PET and CT scans using the new probe, they compared its diagnostic accuracy with conventional imaging modalities and other tests.

Their results validated the test's effectiveness, achieving 100% diagnostic accuracy in all 12 participants. Specifically, the probe outperformed CT, MRI, endoscopic ultrasonography, and selective arterial calcium stimulation tests in terms of sensitivity. The new method even successfully detected cases that were difficult to diagnose conclusively through existing methods.

Removal of these lesions confirmed their pathology as insulinomas, and following surgery, all patients experienced complete resolution of hypoglycemic symptoms, demonstrating the clinical effectiveness of the technique.

Beyond insulinoma diagnoses, this imaging method could have potentially broad impact across related medical fields, such as in diagnosing nesidioblastosis and other unexplained hypoglycemia, and even in assessing disease progression in diabetes.

"Ultimately, we aim for international clinical adoption of this treatment to reduce patient burden and enhance diagnostic accuracy for insulinoma, as well as support staging and disease characterization in diabetes worldwide," says Murakami.

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The paper "Qualitative and Quantitative Analyses of Noninvasive Diagnosis of Insulinoma Using [¹⁸F]FB(ePEG12)12-exendin-4 PET/CT" appeared on 20 May 2025 in The Journal of Clinical Endocrinology & Metabolism, with doi: 10.1210/clinem/dgaf253

About Kyoto University

Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at undergraduate and graduate levels complements several research centers, facilities, and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en